Health

Scientific publication

Dermal PK/PD of a lipophilic topical drug in psoriatic patients by continuous intradermal membrane-free sampling

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Manfred Bodenlenz, Höfferer C., Dr Christoph Magnes, Dr Roland Schaller-Ammann, Schaupp L, Dr Franz Feichtner, Ratzer M, Dr Karin Pickl, Dr Frank Sinner, Wutte A., Korsatko S., Köhler G., Legat F., Benfeldt E., Wright A., Neddermann D., Jung T., Prof Dr Thomas Pieber,

European Journal of Pharmaceutics and Biopharmaceutics 81 (3):635-641., 2012

Abstract:

BACKGROUND:

Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps.

METHODS:

Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple dOFM sampling was performed for 25 h from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight push-pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis.

RESULTS:

dOFM was well tolerated and demonstrated significant drug concentrations in lesional as well as non-lesional skin after 8 days, but did not show significant differences between tissues. On day 8, TNFα release following probe insertion was significantly reduced compared to day 1.

CONCLUSIONS:

Novel membrane-free probes and wearable multi-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology, and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical setting.